tbuckley/cabot-search huggingface dataset:
Changes in Induced Medical and Procedural Abortion Rates in a Commercially Insured Population, 2018 to 2022
Authors: Catherine S. Hwang, Aaron S. Kesselheim, Ameet Sarpatwari, Krista F. Huybrechts, Gregory Brill, Benjamin N. Rome
Journal: Annals of Internal Medicine (2023)

During the COVID-19 pandemic, access to in-person care was limited, and regulations requiring in-person dispensing of mifepristone for medical abortions were relaxed. The effect of the pandemic and accompanying regulatory changes on abortion use is unknown.To estimate changes in the incidence rate of induced medical and procedural abortions.Serial cross-sectional study with interrupted time-series analyses.Commercially insured persons in the United States.Reproductive-aged women.Onset of the COVID-19 pandemic in March 2020 and subsequent regulatory changes affecting the in-person dispensing requirement for mifepristone.Monthly age-adjusted incidence rates of medical and procedural abortions were measured among women aged 15 to 44 years from January 2018 to June 2022. Medical abortions were classified as in-person or telehealth. Linear segmented time-series regression was used to calculate changes in abortion rates after March 2020.In January 2018, the estimated age-adjusted monthly incidence rate of abortions was 151 per million women (95% CI, 142 to 161 per million women), with equal rates of medical and procedural abortions. After March 2020, there was an immediate 14% decrease in the monthly incidence rate of abortions (21 per million women [CI, 7 to 35 per million women]; P = 0.004), driven by a 31% decline in procedural abortions (22 per million women [CI, 16 to 28 per million women]; P < 0.001). Fewer than 4% of medical abortions each month were administered via telehealth.Only abortions reimbursed by commercial insurance were measured.The incidence rate of procedural abortions declined during the COVID-19 pandemic, and this lower rate persisted after other elective procedures rebounded to prepandemic rates. Despite removal of the in-person dispensing requirement for mifepristone, the use of telehealth for insurance-covered medical abortions remained rare. Amid increasing state restrictions, commercial insurers have the opportunity to increase access to abortion care, particularly via telehealth.Health Resources and Services Administration.
Guiding Intervention for Complex Coronary Lesions by Optical Coherence Tomography or Intravascular Ultrasound
Authors: Do-Yoon Kang, Jung-Min Ahn, Sung-Cheol Yun, Seung-Ho Hur, Yun-Kyeong Cho, Cheol Hyun Lee, Soon Jun Hong, Subin Lim, Sang-Wook Kim, Hoyoun Won, Jun-Hyok Oh, Jeong Cheon Choe, Young Joon Hong, Yong-Hoon Yoon, Hoyun Kim, Yeonwoo Choi, Jinho Lee, Young Won Yoon, Soo-Joong Kim, Jang-Ho Bae, Seung-Jung Park, Duk-Woo Park
Journal: Journal of the American College of Cardiology (2023)
Drugging RAS: Moving Beyond KRASG12C
Journal: Cancer Discovery (2023)

Abstract Preliminary results from phase I trials respectively evaluating RMC-6236, a pan-RAS inhibitor, and HRS-4642, a KRASG12D inhibitor, indicate that both are safe and show promising signs of antitumor activity. These are just two of the candidate RAS therapies in a burgeoning development space as the field looks ahead to drugs that hit more than just KRASG12C.
Glaucoma: neuroprotection with NAD-based therapeutic interventions
Authors: Alberto Chiarugi
Journal: Trends in Pharmacological Sciences (2023)

Clinical evidence shows that intraocular hypertension is not the primary pathogenetic event of glaucoma, whereas early neurodegeneration of retinal ganglion cells (RGCs) represents a key therapeutic target. Unfortunately, failure of clinical trials with neuroprotective agents, in particular those testing the anti-excitotoxic drug memantine, generated widespread skepticism regarding the possibility of counteracting neurodegeneration during glaucoma. New avenues for neuroprotective approaches to counteract glaucoma evolution have been opened by the identification of a programmed axonal degeneration (PAD) program triggered by increased nicotinamide mononucleotide (NMN)/NAD concentration ratio. Positive results of proof-of-concept clinical studies based on sustaining axonal NAD homeostasis facilitated the design of Phase 2/3 trials. Here, I share my opinion on how neurodegeneration in glaucoma should be put into context, together with an appraisal of the pharmacological rationale of NAD-supporting therapies for use during glaucoma progression.
Cost-Utility Analysis of Geriatric Assessment and Management in Older Adults With Cancer: Economic Evaluation Within 5C Trial
Authors: Yeva Sahakyan, Qixuan Li, Shabbir M.H. Alibhai, Martine Puts, Shant T. Yeretzian, Mohammed R. Anwar, Sarah Brennenstuhl, Bianca McLean, Fay Strohschein, George Tomlinson, Aria Wills, Lusine Abrahamyan
Journal: Journal of Clinical Oncology (2023)

Geriatric assessment (GA) is a guideline-recommended approach to optimize cancer management in older adults. We conducted a cost-utility analysis alongside the 5C randomized controlled trial to compare GA and management (GAM) plus usual care (UC) against UC alone in older adults with cancer.
Etiology of Early-Onset Complete Atrioventricular Block and Use of Implanted Cardiac Electronic Devices
Authors: Gilad Margolis, Jennifer Chee, Mark Kazatsker, Ariel Roguin, Christopher Madias, Munther Homoud, Ofer Kobo, Nashed Hamuda, Eran Leshem, Guy Rozen
Journal: Journal of the American College of Cardiology (2023)
Public Out-of-Hospital Cardiac Arrest in Residential Neighborhoods
Authors: Anne Juul Grabmayr, Fredrik Folke, Mads Christian Tofte Gregers, Louise Kollander, Nanna Bo, Linn Andelius, Theo Walter Jensen, Florian Ettl, Mario Krammel, Patrick Sulzgruber, Konstantin A. Krychtiuk, Christian Torp-Pedersen, Annette Kjær Ersbøll, Carolina Malta Hansen
Journal: Journal of the American College of Cardiology (2023)

Although one-half of all public out-of-hospital cardiac arrests (OHCAs) occur outside private homes in residential neighborhoods, their characteristics and outcomes remain unexplored. The authors assessed interventions before ambulance arrival and survival for public OHCA patients in residential neighborhoods. Public OHCAs from Vienna (2018-2021) and Copenhagen (2016-2020) were designated residential neighborhoods or nonresidential areas. Interventions (cardiopulmonary resuscitation [CPR], automated external defibrillator [AED] attached, and defibrillation) and 30-day survival were compared using a generalized estimation equation model adjusted for age and time of day and presented as ORs. We included 1,052 and 654 public OHCAs from Vienna and Copenhagen, respectively, and 68% and 55% occurred in residential neighborhoods, respectively. The likelihood of CPR, defibrillation, and survival in residential neighborhoods vs nonresidential areas (reference) were as follows: CPR Vienna, 73% vs 78%, OR: 0.78 (95% CI: 0.57-1.06), CPR Copenhagen, 83% vs 90%, OR: 0.54 (95% CI: 0.34-0.88), and CPR combined, 76% vs 84%, OR: 0.70 (95% CI: 0.53-0.90); AED attached Vienna, 36% vs 44%, OR: 0.69 (95% CI: 0.53-0.90), AED attached Copenhagen, 21% vs 43%, OR: 0.33 (95% CI: 0.24-0.48), and AED attached combined, 31% vs 44%, OR: 0.53 (95% CI: 0.42-0.65); defibrillation Vienna, 14% vs 20%, OR: 0.61 (95% CI: 0.43-0.87), defibrillation Copenhagen, 16% vs 36%, OR: 0.35 (95% CI: 0.24-0.51), and defibrillation combined, 15% vs 27%, OR: 0.46 (95% CI: 0.36-0.61); and 30-day survival rate Vienna, 21% vs 26%, OR: 0.84 (95% CI: 0.58-1.20), 30-day survival rate Copenhagen, 33% vs 44%, OR: 0.65 (95% CI: 0.47-0.90), and 30-day survival rate combined, 25% vs 36%, OR: 0.73 (95% CI: 0.58-0.93). Two-thirds of public OHCAs occurred in residential neighborhoods with fewer resuscitative efforts before ambulance arrival and lower survival than in nonresidential areas. Targeted efforts to improve early CPR and defibrillation for public OHCA patients in residential neighborhoods are needed.
Real-World Surgical and Endoscopic Recurrence Based on Risk Profiles and Prophylaxis Utilization in Postoperative Crohn’s Disease
Authors: Ravi S. Shah, Salam Bachour, Abel Joseph, Huijun Xiao, Ruishen Lyu, Hareem Syed, Terry Li, Shravya Pothula, Vall Vinaithirthan, Adel Hajj Ali, Sussel Contreras, Jessica H. Hu, Edward L. Barnes, Jordan E. Axelrad, Stefan D. Holubar, Miguel Regueiro, Benjamin L. Cohen, Benjamin H. Click
Journal: Clinical Gastroenterology and Hepatology (2023)

Preoperative risk stratification may help guide prophylactic biologic utilization for the prevention of postoperative Crohn's disease (CD) recurrence; however, there are limited data exploring and validating proposed clinical risk factors. We aimed to explore the preoperative clinical risk profiles, quantify individual risk factors, and assess the impact of biologic prophylaxis on postoperative recurrence risk in a real-world cohort.
Risk Factors for Reintervention With Functionally Single-Ventricle Disease Undergoing Staged Palliation in England and Wales: A Retrospective Cohort Study
Authors: Qi Huang, Deborah Ridout, Victor Tsang, Nigel E. Drury, Timothy J. Jones, Hannah Bellsham-Revell, Elena Hadjicosta, Anna N. Seale, Chetan Mehta, Christina Pagel, Sonya Crowe, Ferran Espuny-Pujol, Rodney C.G. Franklin, Kate L. Brown
Journal: Circulation (2023)
Innovation in the Delivery of Behavioral Health Services
Authors: Thomas D'Aunno, Charles J. Neighbors
Journal: Annual Review of Public Health (2023)

Several factors motivate the need for innovation to improve the delivery of behavioral health services, including increased rates of mental health and substance use disorders, limited access to services, inconsistent use of evidence-based practices, and persistent racial and ethnic disparities. This narrative review identifies promising innovations that address these challenges, assesses empirical evidence for the effectiveness of these innovations and the extent to which they have been adopted and implemented, and suggests next steps for research. We review five categories of innovations: organizational models, including a range of novel locations for providing services and new ways of organizing services within and across sites; information and communication technologies; workforce; treatment technologies; and policy and regulatory changes. We conclude by discussing the need to strengthen and accelerate the contributions of implementation science to close the gap between the launch of innovative behavioral health services and their widespread use.
Obesity and its comorbidities, current treatment options and future perspectives: Challenging bariatric surgery?
Authors: Simon Kloock, Christian G. Ziegler, Ulrich Dischinger
Journal: Pharmacology & Therapeutics (2023)

Obesity and its comorbidities, including type 2 diabetes mellitus, cardiovascular disease, heart failure and non-alcoholic liver disease are a major health and economic burden with steadily increasing numbers worldwide. The need for effective pharmacological treatment options is strong, but, until recently, only few drugs have proven sufficient efficacy and safety. This article provides a comprehensive overview of obesity and its comorbidities, with a special focus on organ-specific pathomechanisms. Bariatric surgery as the so far most-effective therapeutic strategy, current pharmacological treatment options and future treatment strategies will be discussed. An increasing knowledge about the gut-brain axis and especially the identification and physiology of incretins unfolds a high number of potential drug candidates with impressive weight-reducing potential. Future multi-modal therapeutic concepts in obesity treatment may surpass the effectivity of bariatric surgery not only with regard to weight loss, but also to associated comorbidities.
Toward Explainable Artificial Intelligence for Precision Pathology
Authors: Frederick Klauschen, Jonas Dippel, Philipp Keyl, Philipp Jurmeister, Michael Bockmayr, Andreas Mock, Oliver Buchstab, Maximilian Alber, Lukas Ruff, Grégoire Montavon, Klaus-Robert Müller
Journal: Annual Review of Pathology Mechanisms of Disease (2023)

The rapid development of precision medicine in recent years has started to challenge diagnostic pathology with respect to its ability to analyze histological images and increasingly large molecular profiling data in a quantitative, integrative, and standardized way. Artificial intelligence (AI) and, more precisely, deep learning technologies have recently demonstrated the potential to facilitate complex data analysis tasks, including clinical, histological, and molecular data for disease classification; tissue biomarker quantification; and clinical outcome prediction. This review provides a general introduction to AI and describes recent developments with a focus on applications in diagnostic pathology and beyond. We explain limitations including the black-box character of conventional AI and describe solutions to make machine learning decisions more transparent with so-called explainable AI. The purpose of the review is to foster a mutual understanding of both the biomedical and the AI side. To that end, in addition to providing an overview of the relevant foundations in pathology and machine learning, we present worked-through examples for a better practical understanding of what AI can achieve and how it should be done.
ENPP1 in Blood and Bone: Skeletal and Soft Tissue Diseases Induced by ENPP1 Deficiency
Authors: Carlos R. Ferreira, Thomas O. Carpenter, Demetrios T. Braddock
Journal: Annual Review of Pathology Mechanisms of Disease (2023)

The enzyme ectonucleotide pyrophosphatase/phosphodiesterase 1 ( ENPP1) codes for a type 2 transmembrane glycoprotein that hydrolyzes extracellular ATP to generate pyrophosphate (PP i ) and adenosine monophosphate, thereby contributing to downstream purinergic signaling pathways. The clinical phenotypes induced by ENPP1 deficiency are seemingly contradictory and include early-onset osteoporosis in middle-aged adults and life-threatening vascular calcifications in the large arteries of infants with generalized arterial calcification of infancy. The progressive overmineralization of soft tissue and concurrent undermineralization of skeleton also occur in the general medical population, where it is referred to as paradoxical mineralization to highlight the confusing pathophysiology. This review summarizes the clinical presentation and pathophysiology of paradoxical mineralization unveiled by ENPP1 deficiency and the bench-to-bedside development of a novel ENPP1 biologics designed to treat mineralization disorders in the rare disease and general medical population.
Gluten-related Disorders From Bench to Bedside
Authors: Claire L Jansson-Knodell, Alberto Rubio-Tapia
Journal: Clinical Gastroenterology and Hepatology (2023)

CD, NCGS, and wheat allergy share some similarities, but exhibit important clinical differences (Table 3). Their multiple possible presentations make diagnosis difficult, and therapy being dietary, without a pharmacologic option, leads to challenges in treatment. When approaching a patient in clinic with gluten-related symptoms, consider the differential diagnosis including CD, NCGS, and wheat allergy. Recall the definitions covered in this narrative review, consider the likelihood of diagnosis given epidemiology, and characterize their clinical phenotype. Perform a proper and guideline-directed evaluation for CD (Figure 2); only after this status is known, implement dietary measures accordingly. Finally, follow these patients clinically for symptomatic improvement, development of complications, concomitant-related conditions, and routine high-quality care.Table 3Comparison of CD and NCGSCDNCGSWheat allergyDescriptionImmune-mediated enteropathyNon-allergic, immune reaction to glutenAllergic, immune-mediatedEpidemiology1%?0.2%PathophysiologyInnate and adaptive immune response to glutenUnclear, innate immune response, increased toll-like receptor expressionIgE-mediated responseSymptom onsetDays to weeksHours to daysMinutes to hoursConsequencesVillous atrophy (decrease in the villous height to crypt depth ratio below the normal range of 3-5:1), increased IELs (>25 IELs per 100 epithelial cells), damage to the small intestine, long-term complicationsNo villous atrophy, may have increased IELs or normal histology in small intestineNo villous atrophy, some cases result in anaphylaxisGluten ingestionRequired to trigger responseLikely required to trigger responseWheat required to trigger allergic responseGeneticsHLA DQ2/DQ8 requiredVariable, no requirementNo requirementDiagnosisSerology and duodenal biopsyEvaluation of response to 6 weeks of GFD and 2 weeks of placebo/gluten challengeaSalerno criteria for research and clinical trials (less helpful in clinical practice).Serum wheat IgE, skin prick testing, evaluation by allergistTreatmentStrict GFDLimiting gluten in diet to tolerated amountEpinephrine pen, avoidanceCD, Celiac disease; GFD, gluten-free diet; HLA, human leukocyte antigen; IELs, intraepithelial lymphocytes; IgE, immunoglobulin E; NCGS, non-celiac gluten sensitivity.a Salerno criteria for research and clinical trials (less helpful in clinical practice). Open table in a new tab
Informing Public Health Policies with Models for Disease Burden, Impact Evaluation, and Economic Evaluation
Authors: Mark Jit, Alex R. Cook
Journal: Annual Review of Public Health (2023)

Conducting real-world public health experiments is often costly, time-consuming, and ethically challenging, so mathematical models have a long-standing history of being used to inform policy. Applications include estimating disease burden, performing economic evaluation of interventions, and responding to health emergencies such as pandemics. Models played a pivotal role during the COVID-19 pandemic, providing early detection of SARS-CoV-2’s pandemic potential and informing subsequent public health measures. While models offer valuable policy insights, they often carry limitations, especially when they depend on assumptions and incomplete data. Striking a balance between accuracy and timely decision-making in rapidly evolving situations such as disease outbreaks is challenging. Modelers need to explore the extent to which their models deviate from representing the real world. The uncertainties inherent in models must be effectively communicated to policy makers and the public. As the field becomes increasingly influential, it needs to develop reporting standards that enable rigorous external scrutiny.
A Phase 1b Study of Ivonescimab, a Programmed Cell Death Protein-1 and Vascular Endothelial Growth Factor Bispecific Antibody, as First- or Second-Line Therapy for Advanced or Metastatic Immunotherapy-Naive NSCLC
Authors: Lei Wang, Yongzhong Luo, Shengxiang Ren, Zhihong Zhang, Anwen Xiong, Chunxia Su, Jin Zhou, Xinmin Yu, Yanping Hu, Xiaodong Zhang, Xiaorong Dong, Shuyan Meng, Fengying Wu, Xiaoming Hou, Yuanrong Dai, Weifeng Song, Baiyong Li, Zhongmin Maxwell Wang, Yu Xia, Caicun Zhou
Journal: Journal of Thoracic Oncology (2023)

PURPOSE This study aimed to evaluate the safety and efficacy of ivonescimab (a bispecific antibody against programmed death-1 [PD-1] and vascular endothelial growth factor [VEGF]) as first- or second-line monotherapy in advanced immunotherapy naïve non-small-cell lung cancer (NSCLC) patients. METHODS Eligible patients received intravenous ivonescimab 10mg/kg every 3 weeks (Q3W), 20 mg/kg every 2 weeks (Q2W), 20 mg/kg Q3W or 30mg/kg Q3W. The primary endpoints were safety and objective response rate (ORR) per RECIST v1.1. RESULTS At data cutoff (October 5, 2022), 108 patients were enrolled and received ivonescimab. Programmed death ligand-1 (PD-L1) tumor proportion score (TPS) was ≥1% in 74 (68.5%) patients, including 35 (32.4%) with TPS ≥50%. The median follow-up was 10.4 months (range 8.4 to 10.9 months). For all patients, ORR and disease control rate (DCR) were 39.8% and 86.1%, respectively. ORR by TPS was 14.7%, 51.4% and 57.1% in patients with TPS <1%, ≥1%, and ≥50%, respectively. In the 67 PD-L1 positive patients receiving first-line ivonescimab, the ORR was 33.3%, 52.6%, 60.0%, and 75.0% at the doses of 10mg/kg Q3W, 20 mg/kg Q2W, 20 mg/kg Q3W and 30mg/kg Q3W, respectively. Grade ≥3 treatment-related adverse events (TRAEs) were observed in 24 (22.2%) patients. TRAEs leading to treatment discontinuation occurred in 1 (0.9%) patient. TRAEs leading to death occurred in 3 (2.8%) patients with squamous histology. The occurrence of grade ≥3 TRAEs and grade ≥3 bleeding events in squamous versus non-squamous histologies were 25.5% vs. 18.9% and 0.0% vs. 1.9%, respectively. CONCLUSION Ivonescimab monotherapy was well tolerated and demonstrated promising efficacy in patients with advanced or metastatic NSCLC.
Diarrhea After Gastric Surgery: More Than Meets the Eye
Authors: Jintong Chen, Yanni Huang, Chengdang Wang
Journal: Clinical Gastroenterology and Hepatology (2023)

A 57-year-old Chinese man presented with a 10-month history of frequent postprandial diarrhea and a 10-kg weight loss. He had a history of Billroth II partial gastrectomy for duodenal ulcer-related obstruction 6 years ago. He appeared cachectic with a body mass index of 16.3 kg/m2 and he had pitting edema in both lower extremities. His hemoglobin level was 7.8 g/dL (range, 13.0–17.5 g/dL), potassium was 2.82 mmol/L (range, 3.50–5.10 mmol/L), albumin was 1.9 g/dL (range, 3.5–5.0 g/dL), and carcinoembryonic antigen was elevated at 13.4 ng/mL (range, <5.2 ng/L). Stool tests were negative for infectious pathogens. Upper endoscopy showed green feculent material in the stomach remnant, and an unobstructed anastomosis without ulcers (Figure A). Histopathology indicated inflammation without dysplasia. A PET/computed tomography scan suggested inflammation at multiple colon segments and at the gastrointestinal anastomosis. Upper gastrointestinal series with oral contrast revealed early entry of contrast into the transverse colon (Figure B), indicating a gastrocolic fistula. A repeat endoscopy confirmed a fistulous tract near the anastomosis (Figure C, arrows), allowing the gastroscope to meet the colonoscope (Figure D). Initial endoscopic closure of the fistula by applying metal clips and nylon sutures in a purse-string fashion failed; thus, surgical resection of the fistula with partial gastrectomy and colectomy was performed. The patient recovered uneventfully, his diarrhea resolved and he had gained 15 kg in body weight at 6 months of follow-up. Gastrocolic fistulas are a rare post partial gastrectomy complication. Presenting features, such as diarrhea, weight loss, abdominal pain, and elevated carcinoembryonic antigen, are nonspecific, but should heighten suspicion. The fistula can usually be diagnosed by endoscopy and/or imaging. Treatment options vary according to fistula characteristics although surgery is usually required. The authors thank Dejun She for his assistance in interpreting and providing the beautiful radiologic images.
Expanding “Practice-Changing” Belzutifan's Reach in RCC
Journal: Cancer Discovery (2023)

Abstract In the LITESPARK-005 and -003 trials, the HIF-2α inhibitor looks effective in advanced clear-cell renal cell carcinoma, both as monotherapy and in combination with VEGFR tyrosine kinase inhibitors. The results favor expanding belzutifan's use beyond von Hippel-Lindau disease–associated cancers, its only current indication.